19-20624371-G-GA

Position:

• chr19-20624371-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001076675.3(ZNF626):​c.1505_1506insT​(p.Ile503HisfsTer95) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (42309 hom., cov: 0)
  • Exomes 𝑓: 0.72 (197533 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF626	NM_001076675.3	c.1505_1506insT	p.Ile503HisfsTer95	frameshift_variant	4/4	ENST00000601440.6	NP_001070143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF626	ENST00000601440.6	c.1505_1506insT	p.Ile503HisfsTer95	frameshift_variant	4/4	4	NM_001076675.3	ENSP00000469958	P1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 106329 AN: 136752 Hom.: 42310 Cov.: 0

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.812

GnomAD3 exomes AF: 0.429 AC: 33280 AN: 77600 Hom.: 8474 AF XY: 0.426 AC XY: 17201 AN XY: 40388

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.354

Gnomad SAS exome AF: 0.413

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.422

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.723 AC: 487876 AN: 674986 Hom.: 197533 Cov.: 27 AF XY: 0.720 AC XY: 243796 AN XY: 338590

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.670

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.777 AC: 106353 AN: 136848 Hom.: 42309 Cov.: 0 AF XY: 0.777 AC XY: 51457 AN XY: 66244

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.810

Alfa AF: 0.803 Hom.: 3906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35575803; hg19: chr19-20807177;